3-129255135-A-C

Variant names:

• chr3-129255135-A-C
• rs4927912
• NM_016128.4:c.492+58A>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016128.4(COPG1):​c.492+58A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,126,252 control chromosomes in the GnomAD database, including 15,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (6529 hom., cov: 31)
  • Exomes 𝑓: 0.12 (9419 hom.)
• Consequence: COPG1 NM_016128.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0510

Genes affected

COPG1 (HGNC:2236): (COPI coat complex subunit gamma 1) Predicted to enable structural molecule activity. Predicted to be involved in several processes, including Golgi vesicle transport; establishment of Golgi localization; and organelle transport along microtubule. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-129255135-A-C is Benign according to our data. Variant chr3-129255135-A-C is described in ClinVar as [Benign]. Clinvar id is 2688300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COPG1	NM_016128.4	c.492+58A>C		intron_variant	Intron 7 of 23	ENST00000314797.10	NP_057212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COPG1	ENST00000314797.10	c.492+58A>C		intron_variant	Intron 7 of 23	1	NM_016128.4	ENSP00000325002.6
COPG1	ENST00000515725.5	n.751+58A>C		intron_variant	Intron 6 of 22	2
COPG1	ENST00000504350.1	n.*560A>C		downstream_gene_variant		3		ENSP00000426457.1
COPG1	ENST00000509208.1	n.*96A>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34215 AN: 151614 Hom.: 6499 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.119 AC: 115680 AN: 974530 Hom.: 9419 AF XY: 0.119 AC XY: 60023 AN XY: 503300

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0909

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.0835

Gnomad4 NFE exome AF: 0.0995

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.226 AC: 34304 AN: 151722 Hom.: 6529 Cov.: 31 AF XY: 0.221 AC XY: 16368 AN XY: 74128

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.0999

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0895 Hom.: 237

Bravo AF: 0.249

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.3
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4927912; hg19: chr3-128973978; COSMIC: COSV59116074; COSMIC: COSV59116074;